Listeria monocytogenes is a foodborne pathogen known to cross the mucosal barrier. To clarify its role in the pathogenesis of diarrhea we investigated effects of listeriolysin O (LLO), the major virulence factor of L. monocytogenes, on ion secretion and barrier function of human colon cells (HT-29/B6). Besides electrophysiogical and flux measurements in the Ussing chamber we tested for putative signal transducers using inhibitory components. Potential involvement of the Ca-signalling pathway was assessed by FURA-2 imaging.

Results: Mucosal LLO induced a dose-dependent, transient increase in short-circuit current (ISC ) and a decrease of transepithelial resistance (Rt). Tracer flux studies revealed the ISC to be mainly accounted for by active Cl secretion. While the decrease in Rt points to a permeability increase for monovalent ions, mannitol permeability was also increased after LLO addition indicating an unspecific barrier defect for small molecules. FURA-2 measurements and testing for known intracellular transducing signals showed that Ca release from intracellular stores and PKC activation mediate LLO-induced Cl secretion.

Conclusion: Listeriolysin induces active Cl secretion and disturbs epithelial barrier function for small solutes. Thus, the Listeria- induced diarrhea comprises two components, secretory diarrhea and leak flux diarrhea.